Zheng et al.

BMC Infectious Diseases (2019) 19:138

https://doi.org/10.1186/s12879-019-3752-6

DEBATE Open Access

One health insights to prevent the next

HxNy viral outbreak: learning from the
epidemiology of H7N9
Zhe Zheng1, Yi Lu2, Kirsty R. Short5,6 and Jiahai Lu1,3,4*

Abstract
Background: With an increased incidence of viral zoonoses, there is an impetus to strengthen collaborations
between public health, agricultural and environmental departments. This interdisciplinary cooperation, also known
as the ‘One Health’ approach, has received significant support from various stakeholders. However, current efforts
and policies still fall short of those needed for an effective One Health approach towards disease control and
prevention. The avian-origin H7N9 influenza A virus outbreak in China serves as an ideal case study to emphasise
this point.
Discussion: Here, we present the features and epidemiology of human infections with H7N9 influenza virus. At the
early stages of the H7N9 epidemic, there was limited virus surveillance and limited prevention measures implemented
in live poultry markets. As a result, zoonotic infections with H7N9 influenza viruses continued to enlarge in both
numbers and geographic distribution. It was only after the number of human infections with H7N9 influenza virus
spiked in the 5th wave of the epidemic that inter-departmental alliances were formed. This resulted in the rapid control
of the number of human infections. We therefore further discuss the barriers that prevented the implementation of
an effective One Health approach in China and what this means for other emerging, zoonotic viral diseases.
Summary: Effective implementation of evidence-based disease management approaches in China will result in
substantial health and economic gains. The continual threat of avian influenza, as well as other emerging zoonotic viral
infections, emphasizes the need to remove the barriers that prevent the effective implementation of One Health
policies in disease management.
Keywords: H7N9, One health, Zoonosis, Influenza virus, Disease management

Background lack of effective intervention strategies by the agricul-

Human infections with avian influenza virus H7N9 tural departments, led to a large number of viral in-
were first identified in March 2013 in south-eastern fections in poultry and six discreet ‘waves’ of human
China. The virus then spread rapidly to the inner infections [3]. The first H7N9 epidemic wave started
provinces of China. As of March 2nd 2018, 1567 in March and ended in June 2013. In subsequent
laboratory-confirmed cases of human infected with waves (2013–2018), the H7N9 influenza virus infec-
avian influenza A(H7N9) viruses have been reported tion season typically started in October and lasted
to the World Health Organization (WHO), including until the following June. From October 2016 to June
at least 615 deaths (a fatality rate of 39%) [1]. The 2017, the number of human H7N9 influenza virus in-
absence of overt clinical signs in poultry [2], and the fections increased to 759 cases (almost the same as
the sum of the previous four waves) and spread
* Correspondence: lujiahai@mail.sysu.edu.cn
across 23 provinces and 6 municipalities [4]. During
1
School of Public Health, Sun Yat-sen University, Zhongshan 2nd Road, this wave, a highly pathogenic avian influenza (HPAI)
Guangzhou 510080, Guangdong, China virus A (H7N9) was identified in birds from the live
3
Key Laboratory of Tropical Disease Control, Sun Yat-sen University,
Zhongshan 2nd Road, Guangzhou, Guangdong, China
poultry markets in Guangdong [5]. Subsequently,
Full list of author information is available at the end of the article thousands of chickens died as a result of HPAI virus
© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Zheng et al. BMC Infectious Diseases (2019) 19:138 Page 2 of 8

H7N9 infection [6, 7]. These events prompted the Chin- of implementing a rapid and comprehensive One
ese Ministry of Agriculture (MoA) to issue an emergency Health approach for emerging zoonotic infections.
notice, asking to strengthen national H7N9 prevention
and controls [8, 9]. This cross-disciplinary effort from Discussion
numerous government department led to a rapid de- Influenza H7N9 virology
cline in the number of human H7N9 influenza virus Influenza A virus H7N9 is a negative sense RNA virus
infections and only 3 cases have been reported since with two key surface glycoproteins, the haemagglutinin
July 2017 [1]. The comparison between former four (HA) and the neuraminidase (NA). It is capable of
epidemic waves and wave fifth in both human and undergoing both antigenic drift (driven by point muta-
poultry are shown in Fig. 1. tions) and antigenic shift (as a result of co-infection and
Cross-species transmission and the evolution of the genome reassortment). The NA of H7N9 influenza vi-
H7N9 virus from a low pathogenic to high pathogenic ruses isolated from human cases most closely resembles
phenotype emphasizes the importance of One Health that found in migrating birds from South Korea [10]. In
– which is based upon the premise that there is an contrast, the HA of human H7N9 influenza viruses can
intimate relationship between human, animal and be traced back to the HA of an H7N3 influenza virus
environmental health. Only when we maintain this from domestic ducks [11]. Typically, the HA of avian in-
broader perspective can we hope to prevent the next fluenza viruses shows a strong preference to bind to
endemic/pandemic with an HxNy influenza virus. In α-2,3 linked sialic acids whilst the HA of human influ-
this article, we will use the outbreak of H7N9 influ- enza viruses typically binds to α-2,6 linked sialic acid
enza viruses in humans as an example of the benefits [12]. Since the upper respiratory tract of humans is rich

Fig. 1 Number of reported human cases and positive virological samples from birds or the environment, by province and origin as of March 2018.
Data include both high and low pathogenic H7N9 viruses. The yellow charts indicate the number of positive virological samples from birds or the
environment of the total of the first four waves. The orange charts indicate that of the five waves. The shallow green charts stand for the number of
the total reported human cases of the first four waves and the deep green ones stand for that of the five waves. The five waves almost count the sum
up of the first four waves both in human and animal. Poultry data comes from FAO [53]. Human data comes from WHO [1]
Zheng et al. BMC Infectious Diseases (2019) 19:138 Page 3 of 8

in α-2,6 receptors, human influenza viruses are well provinces [4]. Three distinct stages were noted during
adapted for efficient human-to-human transmission [13]. the H7N9 influenza virus epidemic. The first stage was
However, via the introduction of point mutations in viral characterized by sporadic human infections with the
HA (Q226L/I, G186 V), the avian H7N9 influenza virus virus (waves one to four of the epidemic). However,
increased its avidity to human receptors [13]. Thus, it since October 2017, once the virus became established
breached the species barrier and was able to spread from in poultry populations across China, the number of hu-
poultry to humans [14–16]. By retaining its ability to man H7N9 influenza virus cases surged. This second
bind to α-2,3 linked sialic acid, the virus predominately stage was associated with a reduction in the mean pa-
replicated in the lower respiratory tract, limiting the effi- tient age, suggesting that a larger proportion of the
cacy of person-to-person spread [17]. This dual receptor population was at risk [25–27]. Fortunately, following a
specificity allowed the virus to continue to circulate in joint effort by animal and public health authorities, both
poultry, including chickens and quails [18, 19]. human and poultry infections were controlled, and the
In the first four waves of the H7N9 outbreak, the cleav- number of human cases remains limited (Fig. 2).
age site of the viral HA possessed only a single amino acid Among all human H7N9 influenza virus infections re-
R (arginine), indicating a low pathogenic phenotype in corded to date, almost 50% of cases have occurred in in-
poultry [11, 20]. However, in viruses isolated from live dividuals over the age of 60. It is also striking to note
poultry markets (LPM) in Guangdong province during the that the majority of infections have occurred in males.
fifth wave, researchers found four amino acids (RKRT) Retired individuals are likely to have a higher risk of
inserted into the HA cleavage site (4 of 69 strains). This virus exposure, as the elderly frequently visit LPMs. In-
insertion was associated with the conversion of the virus deed, approximately 80% of patients exposed to poultry
from a low to high pathogenic phenotype in poultry [21]. did so at a LPM, whilst occupational exposure only
Moreover, an increased number of virus strains with a accounted for approximately 10% of patients [3, 28, 29].
588 V mutation in the PB2 were detected [22]. The 588 V The role of LPMs in the zoonotic spread of H7N9 influ-
mutation has previously been associated with enhanced enza viruses is further supported by the fact that positive
viral pathogenesis in mammalian species [22, 23]. Indeed, viral samples are most commonly isolated from chickens
there were at least 23 different genotypes of H7N9 influ- sold in LPMs [30]. Moreover, sequence analysis of H7N9
enza viruses detected by the end of December 2017. viruses isolated from LPMs suggests that poultry are the
Among those, seven genotypes were genetically distinct, most likely source of human infections [11]. This is con-
whilst 16 were found to have evolved from the 2013 sistent with experimental studies showing that H7N9
H7N9 influenza viruses [21]. Although the HPAI virus virus titers are higher in quails and chickens (when com-
H7N9 was first isolated from LPMs in Guangdong, it is pared to other poultry), and only these two species can
believed that the HPAI virus H7N9 originated from the efficiently transmit the virus through direct contact [31].
Yangtze river delta and spread to the southeast coast via In contrast, pigs are unable to sufficiently transmit the
live poultry transactions [24]. The HPAI virus H7N9 then H7N9 influenza virus after experimental infection [18].
evolved into multiple genotypes via reassortment with Poultry appeared to have played a particularly significant
H9N2 influenza viruses and local low pathogenic H7N9 role in the H7N9 epidemic outbreak as they surpassed
viruses [24]. As of July 2017, the HPAI H7N9 influenza human-source predictors to be the dominant factor in
virus has spread to more than 12 different provinces in disease outbreaks [23].
China [24].
H7N9 prevention and control measures in China
Epidemiology of human infections with H7N9 influenza During the first four waves of the epidemic, the H7N9
viruses virus was classified as a LPAI virus and caused no overt
Since February 2013, six waves of human H7N9 influ- clinical symptoms in poultry. This impeded attempts to
enza virus infections have occurred in China. The total develop accurate viral surveillance [32]. Moreover, in
number of human infections has varied dramatically be- light of the associated economic losses, some agricul-
tween waves, ranging from 134 cases in the first wave to tural authorities and members of the poultry industry
781 cases in the fifth wave. Only 3 cases have been re- contested the conclusion that poultry were the source of
ported since October 2017 to present day (i.e during the human infections [33]. These individuals emphasized
sixth wave). Like other influenza virus strains, the H7N9 that there was insufficient evidence to prove that the
influenza virus showed increased circulation amongst poultry were the original source of the virus [34]. It was
both poultry and humans in winter and spring months, further argued that the H7N9 influenza virus should nei-
in particular from December to April. In China, more ther be named as avian influenza nor should the govern-
than half of the reported cases have been concentrated ment report every human infection to the general public
in Zhejiang (310), Guangdong (258) and Jiangsu (251) [34, 35]. This dissent represented a significant obstacle
Zheng et al. BMC Infectious Diseases (2019) 19:138 Page 4 of 8

Fig. 2 H7N9 virus origin and its development. a illustrates the current H7N9 epidemic. Sequencing analyses revealed that the human
infections with H7N9 virus came from three avian origins, with six internal genes from avian influenza A (H9N2) viruses in domestic
poultries, the hemagglutinin (HA) gene from AI H7N3 in domestic ducks and the neuraminidase (NA) gene mutate from AI H7N9 in
migrating birds reservoir [11]. After they recombined and mutated into the novel LPAI H7N9 virus that can infect poultry with little to
no disease in poultry, it came into the human-animal interface and then gained the power to cross the species barrier. Causing four
epidemic waves in human and poultry, the H7N9 transmit wider in the chicken reservoir, adding the opportunities to mutate and
recombine. With genetic mutation, H7N9 virus amplify among both poultry and human population in the five wave. b illustrates the
control benefits we would gain if implement One Health policy

for information transparency and inter-departmental virus from patients and tested aerosol samples from
collaboration. LPMs [39, 40]. The control strategies used at LPMs
When human infections with the H7N9 influenza during this time included flushing once per day, steriliz-
virus were first identified, control strategies focused on ing once per week and closing once per month so that a
patient isolation and health education [36]. As more thorough disinfection process could be carried out [41].
information became available about the transmission of LPMs were also closed when human and/or poultry
the H7N9 virus, disease control departments focused on cases were reported. After the HPAI virus H7N9 was
strengthening disease prevention and surveillance identified and caused significant poultry morbidity and
amongst poultry industry workers, enhancing the sanita- mortality, animal and public health authorities organized
tion of LPMs and improving hygiene during poultry various conferences to bring together veterinary,
slaughter and transactions [37, 38]. Simultaneously, the epidemiology and virology experts. These conferences
MoA established active surveillance in animals and the helped establish strong inter-departmental collaborations
environment at multiple sites whilst the Chinese Centers to prevent and control the spread of H7N9 influenza vi-
of Disease Control (CDC) isolated and identified the ruses [42]. This approach proved to be highly successful
Zheng et al. BMC Infectious Diseases (2019) 19:138 Page 5 of 8

and only 3 cases of human infection with H7N9 influ- serology samples is much higher in LPMs than farms,
enza virus were reported in the last wave (Fig. 3). agricultural departments may neglect this dual transmis-
sion pattern, resulting in continued infections [30] (Fig. 4).
The one health approach Another impediment to controlling the H7N9 influenza
Today, due to the the increasingly blurry human-animal virus outbreak is the protection of sectional interests.
interface, zoonotic infections are increasing at an un- Eliminating avian influenza in poultry represents a signifi-
precedented rate [43]. This interdependence between cant economic loss for the poultry industry. Initially,
human health, animal health, and environmental health farmers and local authorities were reluctant to report
gave rise to the concept of “One Health”, which means avian influenza outbreaks, in particular, the asymptomatic
solving the growing problem of infectious disease via LPAI virus H7N9 cases. Some farmers and small compan-
cooperation between experts in different disciplines [44]. ies even transported infected poultry away from their
As the world’s biggest agricultural country, with a large premises once a viral infection had been identified, further
human-animal interface, China experiences a large facilitating the spread of the virus [49]. The difficulties as-
number of emerging infectious zoonotic diseases, [45, 46]. sociated with monitoring/preventing short distance, live
This feature makes China the ideal setting for the imple- poultry transportations potentially contributed to the re-
mentation of a One Health policy and to effectively ad- peated waves of H7N9 influenza virus outbreaks in China.
dress these health challenges. To a certain extent, closing LPMs after the start of an
avian influenza virus epidemic can reduce the risk of
Current impediments human zoonotic infections [50]. However, such an ap-
China plays a vital role in the international poultry trade proach should only be viewed as a temporary measure
[47]. However, 30% of the poultry raised in China are as it does not eliminate the source of the infection.
raised in backyard conditions without any biosecurity [48]. Moreover, LPMs form an integral part of some people’s
This widespread use of backyard farms makes it challen- livelihood and it would be unrealistic to permanently
ging for the MoA to conduct routine avian diseases sur- close LPMs. Moreover, even if the government banned
veillance. Furthermore, the unique trade model used in live poultry transactions in markets (and only permitted
China, “Company + peasant household”, creates oppor- the sale of frozen chickens) many people would simply
tunities for H7N9 influenza viruses to transmit from sell and buy live poultry on an individual basis. This
poultry farms to wholesale markets, where different would make it even harder to establish a consolidated
genotypes avian influenza viruses can reassort. There is disease control management program and it would
also a risk of reverse virus transmission from LPMs to significantly hamper any efforts to investigate poultry
farms [15, 31]. However, because the rate of positive exposure history [42].

Fig. 3 Government measures time-line. Agricultural departments and public health departments turn from reserved collaboration to
reinforced collaboration
Zheng et al. BMC Infectious Diseases (2019) 19:138 Page 6 of 8

the poultry industry and enhancing farming

support. This could include promoting industrial
transformation and improving cold chain
transportation systems. After early detection of live
poultry infections, culling, disinfection, isolation and
other virus purification measures must be carried
out immediately [52].
(3) Continued active monitoring of the wild bird
reservoirs and intensified virus tracing. Diagnostic
teams in the veterinary system should use high-
throughput viral sequencing to continually monitor
and analyze the diversity of DNA/RNA viruses at
Fig. 4 H7N9 virus transmission routes. H7N9 virus maintain in poultry
reservoirs in farms and backyard. During transportation, virus transmits the human-animal interface. These technologies will
among the large group of live poultries through direct and/or indirect extend the scope of virus surveillance, identify
contact. Arriving at LPMs, immunological naive population exposes to potential emerging infectious diseases and improve
infected poultries and/or H7N9 virus aerosol. Risk groups get affected. early warning capabilities. Establishing such a rapid
Contaminated cages and other staffs may transfer H7N9 virus reversely
virus monitoring and reporting system will facilitate
to farms and backyards and form an infection loop. Frequent clean
and disinfect after each workday could cut down the loop more efficient source control of the disease.
(4) Develop new influenza virus vaccines and antiviral
drugs and prioritize their distribution. This
Using one health to prevent the next HxNy influenza approach should include prioritizing vaccination of
virus outbreak exposed animal workers and domestic animals. This
The prevention and control of H7N9 influenza virus in- requires us to move from the current passive
fections represents an important case-study in One monitoring system in hospitals to the ‘front line’.
Health. During the first few waves of the epidemic, there Stopping and monitoring the infection of those at
was no consolidated, multidisciplinary response and the occupational risk of exposure is essential in
outbreak continued unabated. However, the number of protecting the general population.
human H7N9 virus infections were successfully con-
trolled when all the relevant stakeholders were able to
collaborate and form a united response. New zoonotic Summary
influenza A viruses like the H7N9 virus will continue to Since 2018, through the concerted efforts of the disease
emerge from the human-animal interface. Therefore, we control department and the agricultural sector, the num-
propose the following four ways to strengthen the co- ber of human cases of H7N9 avian influenza virus infec-
operation between agricultural departments and public tion has fallen sharply. This is a clear example of the
health departments in the context of zoonotic disease importance of a One Health strategy in combating zoo-
outbreaks. nosis. To better control H7N9 influenza virus and prevent
the emergence of novel influenza virus strains, we advo-
(1) The early deployment of multi-sectoral joint cate establishing coordination and cooperation among
prevention and control mechanisms is essential in local governments, veterinarians, disease control and mar-
the early detection and control of epidemics. The ket management departments. This will ensure that we
agricultural sector and the disease control are able to effectively meet the constant challenge of
department need to conduct instant information emerging infectious diseases.
interchanges and adopt joint monitoring and
disposal measures. Establishing and improving Abbreviations
CDC: Centers of disease control; HA: Haemagglutinin; HPAI: High pathogenic
animal transportation and supervision mechanisms, avian influenza; LPAI: Low pathogenic avian influenza; LPM: Live poultry
such as animal border inspection and quarantine market; MoA: The Ministry of Agriculture China; NA: Neuraminidase; SA: Sialic
stations in provinces and major cities, will also help acids; WHO: World Health Organization
to avoid the ongoing spread of the disease [51].
(2) Strengthened biosecurity (i.e. segregation, cleaning Acknowledgements
We thank Zhenyu Lin, for revising the manuscript.
and disinfection) in both farms and LPMs. This
could include establishing biosecurity isolation
zones to prevent the spread of new avian viruses via Funding
This work was funded by the the National Science and Technology Major
the contact of poultry and wild birds. The Project(2018ZX10101002)and Guangdong Provincial Science and Technology
government should further focus on standardizing Project (2018B020241002).
Zheng et al. BMC Infectious Diseases (2019) 19:138 Page 7 of 8

Availability of data and materials 13. Tumpey TM, Maines TR, Van Hoeven N, Glaser L, Solorzano A, Pappas C,
The datasets used and/or analyzed during the current study are available Cox NJ, Swayne DE, Palese P, Katz JM, et al. A two-amino acid change in
from the corresponding author on reasonable request. the hemagglutinin of the 1918 influenza virus abolishes transmission.
Science. 2007;315(5812):655–9.
Authors’ contributions 14. Xiong X, Martin SR, Haire LF, Wharton SA, Daniels RS, Bennett MS, McCauley
ZZ and JHL conceived the article and prepared the first draft. KRS and YL JW, Collins PJ, Walker PA, Skehel JJ, et al. Receptor binding by an H7N9
revised and edited the paper. All authors contributed to the drafting of the influenza virus from humans. Nature. 2013;499(7459):496–9.
final version. All authors have read and approved the final manuscript. 15. Wang D, Yang L, Zhu W, Zhang Y, Zou S, Bo H, Gao R, Dong J, Huang W,
Guo J, et al. Two outbreak sources of influenza A (H7N9) viruses have been
Ethics approval and consent to participate established in China. J Virol. 2016;90(12):5561–73.
Not applicable. 16. Schrauwen EJ, Richard M, Burke DF, Rimmelzwaan GF, Herfst S, Fouchier RA.
Amino acid substitutions that affect receptor binding and stability of the
Consent for publication hemagglutinin of influenza A/H7N9 virus. J Virol. 2016;90(7):3794–9.
Not applicable. 17. Benton DJ, Wharton SA, Martin SR, McCauley JW. Role of neuraminidase in
influenza A(H7N9) virus receptor binding. J Virol. 2017;91(11).
Competing interests 18. Pantin-Jackwood MJ, Miller PJ, Spackman E, Swayne DE, Susta L, Costa-Hurtado M,
The authors declare that they have no competing interests. Suarez DL. Role of poultry in the spread of novel H7N9 influenza virus in China.
J Virol. 2014;88(10):5381.
19. Zhang Q, Shi J, Deng G, Guo J, Zeng X, He X, Kong H, Gu C, Li X, Liu J, et al.
Publisher’s Note H7N9 influenza viruses are transmissible in ferrets by respiratory droplet.
Springer Nature remains neutral with regard to jurisdictional claims in
Science. 2013;341(6144):410.
published maps and institutional affiliations.
20. Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, Chen J, Jie Z, Qiu H, Xu K, et al.
Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl
Author details
1 J Med. 2013;368(20):1888–97.
School of Public Health, Sun Yat-sen University, Zhongshan 2nd Road,
21. Shi J, Deng G, Kong H, Gu C, Ma S, Yin X, Zeng X, Cui P, Chen Y, Yang H,
Guangzhou 510080, Guangdong, China. 2Department of Environmental
et al. H7N9 virulent mutants detected in chickens in China pose an increased
Health Sciences, School of Public Health, University at Albany, State
threat to humans. Cell Res. 2017;27(12):1409–21.
University of New York, 1 University Place, Rensselaer, NY 12144, USA. 3Key
Laboratory of Tropical Disease Control, Sun Yat-sen University, Zhongshan 22. Xiao C, Ma W, Sun N, Huang L, Li Y, Zeng Z, Wen Y, Zhang Z, Li H, Li Q,
2nd Road, Guangzhou, Guangdong, China. 4One Health Center of Excellence et al. PB2-588 V promotes the mammalian adaptation of H10N8, H7N9 and
for Research &Training, Zhongshan 2nd Road, Guangzhou, Guangdong, H9N2 avian influenza viruses. Sci Rep. 2016;6:19474.
China. 5School of Chemistry and Molecular Biosciences, The University of 23. Li Y, Qi W, Qiao J, Chen C, Liao M, Xiao C. Evolving HA and PB2 genes of
Queensland, QLD, St Lucia 4072, Australia. 6Australian Infectious Diseases influenza a (H7N9) viruses in the fifth wave - increasing threat to both birds
Research Centre, The University of Queensland, QLD, St Lucia 4072, Australia. and humans? J Infect. 2017;75(2):184–6.
24. Yang L, Zhu W, Li X, Chen M, Wu J, Yu P, Qi S, Huang Y, Shi W, Dong J, et al.
Received: 1 June 2018 Accepted: 29 January 2019 Genesis and spread of newly emerged highly pathogenic H7N9 avian viruses
in mainland China. J Virol. 2017;91:23.
25. Han DD, Han CX, Li LY, Wang M, Yang JH, Li M. Epidemiology of human
References infection with avian influenza a(H7N9) virus in China, 2013-2017. Zhonghua
1. Influenza at the human-animal interface, summary and assessment, 26 Liu Xing Bing Xue Za Zhi. 2018;39(1):44–6.
January to 2 March 2018. http://www.who.int/influenza/human_animal_ 26. Hui DSC, Lee N, Chan PKS. Avian influenza A (H7N9) virus infections in
interface/Influenza_Summary_IRA_HA_interface_02_03_2018.pdf?ua=1. humans across five epidemics in mainland China, 2013-2017. J Thorac Dis.
2. Spackman E, Pantin-Jackwood M, Swayne DE, Suarez DL, Kapczynski DR. 2017;9(12):4808–11.
Impact of route of exposure and challenge dose on the pathogenesis of 27. Artois J, Jiang H, Wang X, Qin Y, Pearcy M, Lai S, Shi Y, Zhang J, Peng Z, Zheng J,
H7N9 low pathogenicity avian influenza virus in chickens. Virology. 2015; et al. Changing geographic patterns and risk factors for avian influenza A(H7N9)
477:72–81. infections in humans, China. Emerg Infect Dis. 2018;24(1):87–94.
3. Zhou L, Ren R, Yang L, Bao C, Wu J, Wang D, Li C, Xiang N, Wang Y, Li D, et 28. Peng W, Zhibin P, Fang VJ, Luzhao F, Tsang TK, Hui J, Lau EHY, Juan Y, Jiandong Z,
al. Sudden increase in human infection with avian influenza A(H7N9) virus Ying Q, et al. Human infection with influenza A(H7N9) virus during 3 major
in China, September-December 2016. Western Pac Surveill Response J. 2017; epidemic waves, China, 2013-2015. Emerg Infect Dis. 2016;22(6):964–72.
8(1):6–14. 29. Guo Z, Xiao D, Li D, Wang Y, Yan T, Dai B, Wang X. The temporal
4. Respiratory Disease Office CfHPotDoH. Avian influenza report. In. Edited by distribution of new H7N9 avian influenza infections based on laboratory-
Respiratory disease office CfHPotDoH, vol. 13; 2017. confirmed cases in mainland China, 2013-2017. Sci Rep. 2018;8(1):4051.
5. OIE. Highly pathogenic avian influenza, China (People’s Rep. of): World 30. H7N9 situation update. http://www.fao.org/ag/againfo/programmes/en/
Organisation for Animal Health; 2017. empres/H7N9/situation_update.html.
6. Huang J, Wang C, Zhou Z. Highly pathogenic avian influenza H7N9 31. Pantin-Jackwood MJ, Miller PJ, Spackman E, Swayne DE, Susta L, Costa-Hurtado M,
diagnostic report in Dongan, Hunan Province. China Poultry. 2017;22:70–2. Suarez DL. Role of poultry in the spread of novel H7N9 influenza virus in China.
7. Highly pathogenic avian influenza, China (People's Rep. of). In: World J Virol. 2014;88(10):5381–90. Accessed 26 Feb 2014.
Organisation for Animal Health: World Organisation for Animal Health. 32. ChinaDaily.2014.H7N9 virus not detected in poultry farms: MOA.2014-01-27.
8. China MoAotPsRo. Eight Measures to strengthen the H7N9 Prevention and http://www.chinadaily.com.cn/china/2014-01/27/content_17261482.htm.
Control. In: Ministry of Agriculture of the People's Republic of China; 2018. 33. Poultry producer wants government to change name of H7N9 avian flu to
9. China MoAotPsRo: National Guidelines for avian influenza H7N9 prevention help restore sales volume & price [https://flutrackers.com/forum/forum/
and control. In. Edited by China MoAotPsRo; 2018. china-h7n9-outbreak-tracking/158234-china-poultry-producer-wants-
10. Liu D, Shi W, Shi Y, Wang D, Xiao H, Li W, Bi Y, Wu Y, Li X, Yan J, et al. Origin government-to-change-name-of-h7n9-avian-flu-to-help-restore-sales-
and diversity of novel avian influenza A H7N9 viruses causing human volume-price-january-15-2014].
infection: phylogenetic, structural, and coalescent analyses. Lancet. 2013; 34. Zhongqiu Zhang, Director of the Department of Veterinary of the Ministry
381(9881):1926–32. of Agriculture, answered the reporter about the prevention and control
11. Chen Y, Liang W, Yang S, Wu N, Gao H, Sheng J, Yao H, Wo J, Fang Q, Cui of the H7N9 avian flu. In: Ministry of Agriculture of People’s Repblic of
D, et al. Human infections with the emerging avian influenza A H7N9 virus China. http://www.gov.cn/gzdt/2014-01/29/content_2578192.htm.
from wet market poultry: clinical analysis and characterisation of viral Accessed 29 Jan 2014.
genome. Lancet. 2013;381(9881):1916–25. 35. China’s poultry industry wants to hush up bird flu news in damage control bid.
12. Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y. Influenza virus http://www.scmp.com/news/china-insider/article/1421319/chinas-poultry-
receptors in the human airway. Nature. 2006;440:435. industry-wants-hush-bird-flu-news-damage-control. Accessed 05 February 2014.
Zheng et al. BMC Infectious Diseases (2019) 19:138 Page 8 of 8

36. National Health Commission of the People’s Republic of China. Human

infection with H7N9 Prevention and Control Plan (First Version). 2013.
http://www.gov.cn/fwxx/jk/2013-04/08/content_2372214.htm. Accessed 08
April 2013.
37. National Health Commission of the People’s Republic of China. Human
infection with H7N9 Prevention and Control Plan (Second Version). 2013.
http://www.nhfpc.gov.cn/yjb/bmdt/201305/
db67c907edd7409d8e4eeb7b638a65fc.shtml. Accessed 10 May 2013.
38. National Health Commission of the People’s Republic of China. Human
infection with H7N9 Prevention and Control Plan (Third Version). 2014.
http://www.moh.gov.cn/zwgk/wtwj/201401/
8c1828375a7949cd85454a76bb84f23a.shtml. Accessed 29 Jan 2014.
39. Ministry of Agriculture of People’s Republic of China. H7N9 Weed Out Plan.
2014. http://www.moa.gov.cn/govpublic/SYJ/201406/t20140625_3950377.
htm. Accessed 25 June 2014.
40. Ministry of Agriculture of People’s Republic of China. H7N9 surveillance
situation. http://www.syj.moa.gov.cn/dwyqdt/jczt/.
41. National Guidelines on the Prevention and Control of H7N9 Influenza in
Poultry. In. Edited by China MoAaRAoPsRo; 2018.
42. The Chinese center for disease control and prevention Cahaec. Consultation
conclusion on prevention and control of human infection with avian
influenza A (H7N9) virus in China from experts of health and agriculture/
veterinary departments. Disease Surveillance. 2017;32(8):623–4.
43. Cleaveland S, Laurenson MK, Taylor LH. Diseases of humans and their
domestic mammals: pathogen characteristics, host range and the risk of
emergence. Philos Trans R Soc Lond Ser B Biol Sci. 2001;356(1411):991–9.
44. Association AVM: One health :a new professional imperative. 2008.
45. Jones KE, Patel NG, Levy MA, Storeygard A, Balk D, Gittleman JL, Daszak P.
Global trends in emerging infectious diseases. Nature. 2008;451:990.
46. Wu J, Liu L, Wang G, Lu J. One health in China. Infect Ecol Epidemiol. 2016;
6:–33843.
47. China: Poultry and Products Semi-annual. In. Edited by Agriculture USDo.
United States Department of Agriculture, Foreign Agriculture Service; 2017.
48. Chendong Pi ZR, Horowitz S. Fair or fowl? Industrialization of poultry
production in China. In: Shefali Sharma BL, editor. Global Meat Complex: The
China Series: Institute for Agriculture and Trade Policy.
49. Li R, Zhang T, Bai Y, Li H, Wang Y, Bi Y, Chang J, Xu B. Live poultry trading
drives China’s H7N9 viral evolution and geographical network propagation.
Front Public Health. 2018;6:210.
50. Yu H, Wu JT, Cowling BJ, Liao Q, Fang VJ, Zhou S, Wu P, Zhou H, Lau EHY,
Guo D, et al. Effect of closure of live poultry markets on poultry-to-person
transmission of avian influenza A H7N9 virus: an ecological study. Lancet.
2014;383(9916):541–8.
51. Lam TT, Zhou B, Wang J, Chai Y, Shen Y, Chen X, Ma C, Hong W, Chen Y,
Zhang Y, et al. Dissemination, divergence and establishment of H7N9
influenza viruses in China. Nature. 2015;522(7554):102–5.
52. Xavier Roche LS, von Dobschuetz S, Akiko Kamata YQ, Beibei Jia GF, Tago D,
Brioudes A, Kalpravidh W, Julio Pinto ER, Lubroth J, Chen J. Chinese-origin
H7N9 avian influenza spread in poultry and human exposure. In: vol. 4.
Food and Agriculture Organization of the United Nations: FAO; 2018.
53. H7N9 situation update. http://www.fao.org/ag/againfo/programmes/en/
empres/h7n9/wave_6/Situation_update_2018_03_28.html. 2018. Accessed
28 March 2018.